Radanyi C, Chambraud B, Baulieu E E
Institut National de la Santé et de la Recherche Médicale (U33), Bicêtre, France.
Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11197-201. doi: 10.1073/pnas.91.23.11197.
A protein of apparent molecular mass of approximately 59 kDa of the FK506-binding protein class (FKBP59) has been found associated with the heat shock protein hsp90 included in nontransformed steroid receptor complexes and termed FKBP59-HBI (HBI for Heat shock protein 90 Binding Immunophilin). Further data analysis has revealed that this immunophilin also belongs to the tetratricopeptide repeat family of proteins. In this work, we describe the hsp90-binding domain of FKBP59-HBI. Density gradient centrifugation, gel filtration, and immunoadsorption analyses failed to demonstrate a stable association between FKBP59-HBI and hsp90 in the rabbit reticulocyte lysate. Using a gel-retardation assay, we provide evidence for a specific ATP-independent interaction between highly purified wild-type rabbit FKBP59-HBI and human hsp90 beta. This interaction was not affected by the immunosuppressants FK506 and rapamycin. Examination of the behavior of several mutants led us to conclude that the tetratricopeptide motifs localized in the C-terminal part of FKBP59-HBI are necessary for hsp90 binding.
已发现一种表观分子量约为59 kDa的FK506结合蛋白家族（FKBP59）的蛋白质与未转化的类固醇受体复合物中包含的热休克蛋白hsp90相关，并将其命名为FKBP59 - HBI（HBI代表热休克蛋白90结合亲免素）。进一步的数据分析表明，这种亲免素也属于四肽重复蛋白家族。在这项工作中，我们描述了FKBP59 - HBI的hsp90结合结构域。密度梯度离心、凝胶过滤和免疫吸附分析未能证明兔网织红细胞裂解物中FKBP59 - HBI与hsp90之间存在稳定的关联。使用凝胶阻滞分析，我们提供了高度纯化的野生型兔FKBP59 - HBI与人类hsp90β之间特异性的、不依赖ATP的相互作用的证据。这种相互作用不受免疫抑制剂FK506和雷帕霉素的影响。对几种突变体行为的研究使我们得出结论，位于FKBP59 - HBI C末端部分的四肽基序对于hsp90结合是必需的。
